Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms

Background: 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) and harmaline are indolealkylamine (iaa) drugs often abused together. our recent studies have revealed the significant effects of co-administered harmaline,a monoamine oxidase inhibitor (maoi),on 5-meo-dmt pharmacokinetics and thermoregulation. this study was to delineate the impact of harmaline and 5-meo-dmt on home-cage activity in mouse models,as well as the contribution of serotonin (5-ht) receptors. methods: home-cage activities of individual animals were monitored automatically in the home cages following implantation of telemetry transmitters and administration of various doses of iaa drugs and 5-ht receptor antagonists. area under the effect curve (auec) of mouse activity values were calculated by trapezoidal rule. results: high dose of harmaline (15 mg/kg,ip) alone caused an early-phase (0-45 min) hypoactivity in mice that was fully attenuated by 5-ht1a receptor antagonist way-100635,whereas a late-phase (45-180 min) hyperactivity that was reduced by 5-ht2a receptor antagonist mdl-100907. 5-meo-dmt (10 and 20 mg/kg,ip) alone induced biphasic effects,an early-phase (0-45 min) hypoactivity that was completely attenuated by way-100635,and a late-phase (45-180 min) hyperactivity that was fully suppressed by mdl-100907. interestingly,co-administration of maoi harmaline (2-15 mg/kg) with a subthreshold dose of 5-meo-dmt (2 mg/kg) induced excessive hyperactivities at late phase (45-180 min) that could be abolished by either way-100635 or mdl-100907. conclusions: co-administration of maoi with 5-meo-dmt provokes excessive late-phase hyperactivity,which involves the activation of both 5-ht1a and 5-ht2a receptors. © 2016 institute of pharmacology,polish academy of sciences. published by elsevier sp. z o.o. all rights reserved.